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Annals of biomedical engineering 08/2011; · 2.41 Impact Factor
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ABSTRACT: Clinical studies have shown that drugs delivered intrathecally distribute much faster than can be accounted for by pure molecular diffusion. However, drug transport inside the cerebrospinal fluid (CSF)-filled spinal canal is poorly understood. In this study, comprehensive experimental and computational studies were conducted to quantify the effect of pulsatile CSF flow on the accelerated drug dispersion in the spinal canal. Infusion tests with a radionucleotide and fluorescent dye under stagnant and pulsatile flow conditions were conducted inside an experimental surrogate model of the human spinal canal. The tracer distributions were quantified optically and by single photon emission computed tomography (SPECT). The experimental results show that CSF flow oscillations substantially enhance fluorescent dye and radionucleotide dispersion in the spinal canal experiment. The experimental observations were interpreted by rigorous computer simulations. To demonstrate the clinical significance, the dispersion of intrathecally infused baclofen, an anti-spasticity drug, was predicted by using patient-specific spinal data and CSF flow measurements. The computational predictions are expected to enable the rational design of intrathecal drug therapies.
Annals of biomedical engineering 07/2011; 39(10):2592-602. · 2.41 Impact Factor
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ABSTRACT: Beta oscillations (12-30 Hz) in local field potentials are prevalent in the motor system, yet their functional role within the context of planning a movement is still debated. In this study, a human participant implanted with a multielectrode array in the hand area of primary motor cortex (MI) was instructed to plan a movement using either the second or fourth of five sequentially presented instruction cues. The beta amplitude increased from the start of the trial until the informative (second or fourth) cue, and was diminished afterwards. Moreover, the beta amplitude peaked just prior to each instruction cue and the delta frequency (0.5-1.5 Hz) entrained to the interval between the cues-but only until the informative cue. This result suggests that the beta amplitude and delta phase in MI reflect the subject's engagement with the rhythmically presented cues and work together to enhance sensitivity to predictable and task-relevant visual cues.
Neuron 02/2010; 65(4):461-71. · 14.74 Impact Factor
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ABSTRACT: This paper presents a sensor for monitoring and controlling the volume of the cerebrospinal fluid-filled ventricles of the brain. The measurement principle of the sensor exploits electrical conductivity differences between the cerebrospinal fluid and the brain tissue. The electrical contrast was validated using dog brain tissue. Experiments with prototype sensors accurately measured the volume content of elastically deformable membranes and gel phantoms with conductivity properties made to match human brain. The sensor was incorporated into a fully automatic feedback control system designed to maintain the ventricular volume at normal levels. The experimental conductivity properties were also used to assess the sensor performance in a simulated case of hydrocephalus. The computer analysis predicted voltage drops over the entire range of ventricular size changes with acceptable positional dependence of the sensor electrodes inside the ventricular space. These promising experimental and computational results of the novel impedance sensor with feedback may serve as the foundation for improved therapeutic options for hydrocephalic patients relying on volume sensing, monitoring or active feedback control.
Medical Engineering & Physics 06/2009; 31(7):838-45. · 1.62 Impact Factor
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ABSTRACT: CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinal fluid (CSF) velocities and flow rates in the brain of six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible for pulsatile CSF flow between the cranial and the spinal subarachnoidal spaces. Simulation results include intracranial pressure gradients, solid stresses and strains, and fluid velocities throughout the cranio-spinal system. Computed velocities agree closely with our in vivo CINE-MRI CSF flow measurements. In addition to normal intracranial dynamics, our model captures the transition to acute communicating hydrocephalus. By increasing the value for reabsorption resistance in the subarachnoid villi, our model predicts that the poroelastic parenchyma matrix will be drained and the ventricles enlarge despite small transmantle pressure gradients during the transitional phase. The poroelastic simulation thus provides a plausible explanation on how reabsorption changes could be responsible for enlargement of the ventricles without large transmantle pressure gradients.
Annals of biomedical engineering 05/2009; 37(7):1434-47. · 2.41 Impact Factor
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ABSTRACT: Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.
Journal of Mathematical Biology 03/2009; 59(6):729-59. · 2.96 Impact Factor
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ABSTRACT: Objective. We evaluated the efficacy of octreotide when administered in a continuous fashion by intrathecal infusion. Materials and Methods. We used a prospective, randomized, controlled, double-blinded method of analysis to evaluate the efficacy of intrathecal octreotide in a population of patients with noncancer pain diagnoses. The patients in this study had an unacceptable response to intrathecal opioids. In the analysis, the patients served as their own controls with a two-armed approach using a phase of treatment with preservative-free saline and a phase of treatment with preservative-free octreotide to assess pain relief. Assessment tools used included visual analog scales and brief pain inventories. Results. Of the 20 patients randomized in the study, 18 completed all data-collection points. One patient withdrew a week after the first refill because of uncontrollable pain, and the other patient withdrew early due to a lack of transportation. Statistical analysis showed no improvement in efficacy in the octreotide arm at the 6-week end-point when compared to saline. No significant differences were seen in any of the other end-points between the saline and intrathecal drug group. Conclusions. Intrathecal octreotide did not show significant improvement in pain relief when compared to saline in chronic noncancer pain. It did show significant relief when compared to baseline, suggesting a positive effect of placebo in the control phase. While the overall data showed no clinical efficacy, a small group of patients did well and continued on the therapy in an open label fashion after the study concluded. These patients had pain consistent with a neuropathic pain diagnosis. The patients had noncancer pain, which was not responsive to intrathecal morphine. The lack of side-effects suggests that the dose selected for the study should be increased for future analysis of this agent, and patients with neuropathic pain should be more closely examined.
Neuromodulation 10/2006; 9(4):284-9. · 1.19 Impact Factor
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ABSTRACT: Introduction. Intrathecal octreotide has been considered an alternative to opioids in chronic infusion for pain. Octreotide is an analog of the growth hormone sandostatin. Previous work has shown the drug to be efficacious in cancer patients who had failed intrathecal opioids. In this study, we examined the safety of intrathecal octreotide in noncancer pain using continuous intrathecal infusion. Methods. We examined 20 patients in a double-blind, prospective, randomized fashion comparing safety and adverse effects using saline or octreotide. Data collected include neurologic examination, adverse effect reporting, and cognitive testing. The study was reviewed and approved by the Saint Francis Hospital Institutional Review Board, which also conducted and approved the authorization to use and disclose protected health information for research purposes which describes the privacy law, Health Insurance Portability and Accountability Act (HIPAA). The Saint Francis Hospital IRB and FDA approved the ongoing use of intrathecal octreotide for research. Conclusions. Intrathecal octreotide, at doses as high as 20 µg/hr, appeared to be as safe as saline when given as a continuous intrathecal infusion. Further work is needed on dose-range analysis and efficacy.
Neuromodulation 07/2005; 8(3):171-5. · 1.19 Impact Factor
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ABSTRACT: Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus.
IEEE Transactions on Biomedical Engineering 05/2005; 52(4):557-65. · 2.28 Impact Factor
